Breaking News: Six Idelalisib Combination Trials Halted

Published on
March 17, 2016

Topics include:
Treatment

After serious adverse events were reported in patients, Gilead Sciences, Inc. has halted six clinical trials using idelalisib (Zydelig) in combination with other drugs. The trials were investigating use of the drug in chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and indolent non-Hodgkin lymphomas (NHL). Leading expert Dr. Jeff Sharman joins Patient Power to explain what happened and what it could mean for patients.

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Dr. Sharman:

Hello. My
name is Jeff Sharman. I am the medical
director of hematology research for the US Oncology Network.

This last week we had some interesting
developments with the molecule idelalisib, also known as Zydelig. This is a medication used in patients with
chronic lymphocytic leukemia and follicular lymphoma, which are the two areas
where it's been approved by the FDA.
What specifically happened this week that was new was that a handful of
clinical trials were stopped abruptly based upon new safety information.

Now, these drugs have been used and again
approved by the FDA on the basis of improvements in outcome, so how come these
studies got closed? Well, it's actually
not the most straightforward explanation, and I'll do my best to unpack
this. In patients with relapsed chronic
lymphocytic leukemia, generally we've seen three clinical trials where
idelalisib led to improvements in outcome.
In at least two of those studies, there is even a survival benefit,
which in CLL is a high bar to prove.

In follicular lymphoma, when we look at those
patients with heavily pretreated and refractory disease, we don't have
comparative studies released just yet, but at least the single-arm studies show
significant favorable impact with idelalisib.
So what changed? Well, the
studies that were terminated were all early-stage studies, generally speaking,
previously untreated CLL or very lightly treated follicular lymphoma.

So why would that be? Well, it may depend when in the treatment
course somebody gets idelalisib. We know
that the target of idelalisib, this molecule called PI3 kinase, is really
important for immune regulation. That
immune regulation may have differential outcome early in the disease versus
late in the disease. So late in the
disease when patients have had lots of prior chemotherapy it may not have as
significant an impact as it does early in the disease.

Now, at ASH 2015, we saw a presentation that
showed frontline use of idelalisib in chronic lymphocytic leukemia was associated
with a very high rate of immune consequences and dysfunction. And what the new
data shows is that not only is there a high level immune dysfunction where you
get high rates of liver function test abnormalities, pneumonitis and so forth,
there is also probably an immunosuppressive effect.

And what I mean by that is that we saw a higher
rate of infectious complications for those patients treated early. So we saw high rates of an unusual viral
infection called CMV, cytomegalovirus, and we also saw this somewhat unusual
lung infection called PCP. It also goes by the name of PJP, there are a handful
of names for it—and this resulted in higher rates of adverse outcomes, serious
adverse events, meaning hospitalizations, and even a few excess deaths.

So as I stand back and look at this, we have a
very discordant picture where it's very clear that late in the disease
idelalisib is associated with very favorable impacts on patient well?being, and
early in the disease it tends to be associated with more adverse events. So I think it helps us to understand perhaps
how to sequence the drugs.

Now, for those patients who are currently on
idelalisib, those patients in clinical trials where the clinical trials have
closed, they're taking patients off the drug.
So I believe there are a total of six clinical trials. And if you're in
a clinical trial with idelalisib, your study site should be able to tell you
right away. For those patients who are
getting idelalisib as a prescription, there should be a discussion about risks
and benefits.

So if you're—early on in the development of the
drug we were commonly trying to prevent PCP infections, and then I think once
the drug got approved it sort of became less of an issue, but now it's an issue
again. So there are ways we can prevent
PCP pneumonia, and you should talk with your doctor about that.

And CMV viruses can cause a variety of unusual
infections, sometimes intestinal infections, sometimes liver infections, lung,
there are a variety of places that can involve this, and so there should be
some monitoring for CMV.

So those are the updates with idelalisib. We again still know that it's an effective
drug in a number of circumstances improving survival, improving outcome later
on in the disease. But early in the disease there's some new safety concerns
that would prevent us from are broad utilization of the medicine.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.